Exercise, the Immune System and Cancer

Question 1

What are the two types of genes that are affected by DNA mutations ?

Answer 1

Tumor suppressor genes

Oncogenes (mitogentic signals) - Promote cell growth

Question 2

What is the name for inherited mutations and acquired mutations

Answer 2

Inherited - Germline

Acquired - Somatic

Question 3

Role of P53

Answer 3

Repair the cell if possible but if severely damage enough caused apoptosis

Question 4

What are the cells that make up a tumor, and what are the most harmful?

Answer 4

Tumor cells, stromal cells and stem cells

cancer stem cells are much more potent.

Question 5

Which innate cells protect against cancer?

Answer 5

NK cells via binding of activatory receptors and subsequent release of secreting granzymes and releasing cytokines for additional support.

Question 6

Which specific cells are anti tumor ?

Answer 6

Dendritic cells
B cells
T cells

Question 7

How does cancer evade the immune system ?

Answer 7

The 3 Es of immunosurveillance:
Elimination – immune system destroys the weakest cancer cells

Equilibrium – small subpopulation survive and lie dormant

Escape – clonal outgrowth of surviving cancer cells

Question 8

What is the intrinsic and extrinsic methods of how cancer evades the immune system

Answer 8

Intrinsic
Loss of antigen
Hidden cell surface antigens
No expression of MHC I or other co-stimulators
Engage inhibitors molecules (e.g. PD-L1)
Secrete factors that suppress anti-tumour immunity (e.g. TGFb)

Extrinsic
Recruit stromal cells with immunomodulatory properties
- Mesenchymal stem cells (MSCs)
- Tumour-associated macrophages promote growth
- Tregs suppress T cell response to tumour
- Myeloid-derived suppressor cells (MDSCs)

Question 9

How can exercise help prevent cancer ?

Answer 9

Sex hormones
Reduced oestrogen in breast cancer survivors
Indirect – via reduction in adiposity

Metabolic hormones
Insulin and insulin growth factor-1 (IGF-1)
Improved insulin sensitivity

Inflammation and adiposity
Chronic inflammation promotes cancer
IL-6, CRP and TNFa

Immune function
Immunodeficiency  increased cancer risk
Moderate intensity exercise  increased T cells, NK cells and neutrophils

Question 10

How can exercise enhance chemo?

Answer 10

Increased vasculature – augmented treatment efficacy

Enhanced drug tolerance – can withstand higher doses

Question 11

Cancer patients who participated in moderate intensity exercise showed ?

Answer 11

Increased NK cell cytotoxic activity
Increased lymphocyte proliferation
Increased numbers of granulocytes
BUT no change in numbers of leukocytes, lymphocytes, NK cells, T lymphocytes, CRP and pro- and anti-inflammatory mediators

Switch from M1 to M2 monocytes - more anti-inflammatory